The following description of the background of the invention is provided simply as an aid in understanding the invention and is not admitted to describe or constitute prior art to the invention.
An approach to cancer therapy and diagnosis involves directing antibodies (Abs) or antibody fragments to disease tissues, wherein the antibody or antibody fragment can target a therapeutic agent to the disease site, i.e., a targeted tissue. A “targeted tissue” is any biological entity (e.g., a system, organ, tissue, cell, organelle, receptor, surface antigen, transmembrane protein, secreted polypeptide, or intracellular component) to which a targetable construct is preferentially delivered. The term “delivered” encompasses being contacted with, bound to, and/or internalized by, a targeted tissue. As used herein, the term “and/or” has the meaning of “and, additionally or alternatively” or “and, in addition to or in the alternative.”
In therapeutic aspects of the invention, the targeted tissue is malignant, infected, inflamed (as in certain autoimmune diseased sites), dysfunctional or displaced or ectopic (e.g., infected cells, cancer cells, endometriosis, etc.), or otherwise diseased (e.g., atherosclerosis, ischemia, clots). Antibodies are used to deliver therapeutic agents to the targeted tissue.
The use of a bsAb/low molecular weight (MW) hapten system is not without some limitations. The arm of the bsAb that binds to the low MW hapten must bind with high affinity, since a low MW hapten is desirably one that clears the living system rapidly when not bound by bsAb. The non-bsAb-bound low MW hapten needs to clear the living system rapidly to avoid non-target tissue uptake and retention. Moreover, the therapeutic agent must remain associated with the low MW hapten throughout its application within the bsAb protocol employed.
This application incorporates by reference the entirety of U.S. application Ser. No. 09/337,756, entitled “Use of bi-specific antibodies for pre-targeting diagnosis and therapy”, which was filed Jun. 22, 1999.
This application incorporates by reference the entirety of U.S. application Ser. No. 09/382,186, entitled “Use of bi-specific antibodies for pre-targeting diagnosis and therapy”, which was filed Aug. 23, 1999.
This application incorporates by reference the entirety of U.S. application Ser. No. 09/823,746, entitled “Production and use of novel peptide-based agents for use with bi-specific antibodies”, which was filed Apr. 3, 2001.
This application incorporates by reference the entirety of U.S. Provisional Application Ser. No. 60/361,037, entitled “Bispecific antibody point mutations for enhancing rate of clearance”, which was filed Mar. 1, 2002.
This application incorporates by reference the entirety of published PCT Application WO 99/66951 by Hansen et al., entitled “Use of bi-specific antibodies for pre-targeting diagnosis and therapy”, which describes some of the reagents used in the Examples herein.
The synthesis of IMP 192 is described in Karacay et al., Experimental pretargeting studies of cancer with a humanized anti-CEA x murine anti-[In-DTPA] bispecific antibody construct and a (99m)Tc-/(188)Re-labeled peptide, Bioconjug. Chem. 11:842-854, 2000.
The radiolabeling of Ac-Phe-Lys(-DTPA)-Tyr-Lys(-DTPA)-NH2 (SEQ ID NO:1) with 111In is described in Boerman et al., Pretargeting of renal cell carcinoma: improved tumor targeting with a bivalent chelate, Cancer Res. 59:4400-4405, 1999.